Renal haemodynamic and protective effects of renoactive drugs in type 2 diabetes: Interaction with SGLT2 inhibitors

Abstract

Diabetic kidney disease remains the leading cause of end‐stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium‐glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post‐glomerular arteriole. People with T2D often receive several different drugs, some of which could also impact the renal vasculature, and could therefore modify both renal efficacy and safety of SGLT2 inhibition. The most commonly prescribed drugs that could interact with SGLT2 inhibitors on renal haemodynamic function include renin‐angiotensin system inhibitors, calcium channel blockers and diuretics. Herein, we review the effects of these drugs on renal haemodynamic function in people with T2D and focus on studies that measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) with gold‐standard techniques. In addition, we posit, based on these observations, potential interactions with SGLT2 inhibitors with an emphasis on efficacy and safety.

Kidney Hemodynamic Effects of Angiotensin Receptor Blockade, Sodium-Glucose Cotransporter-2 Inhibition Alone, and Their Combination: A Crossover Randomized Trial in People With Type 2 Diabetes

“…R enin-angiotensin system (RAS) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors improve kidney outcomes in people with type 2 diabetes. 1 Lowering of glomerular pressure, clinically characterized by an acute estimated glomerular filtration rate (eGFR) decline, contributes to the kidney-protective properties of these drugs. 2 In all trials studying their kidney effects, SGLT2 inhibitors were introduced on top of standard of care, including RAS inhibition.…”

Angiotensin pathways under therapy with empagliflozin in patients with chronic heart failure

“…Large outcome trials in patients with CHF demonstrate that there are no additional safety findings in patients treated with SGLT2 inhibitors and RAS inhibitors. 1 , 2 , 20 Previous studies in patients with T2DM suggest that SGLT2 inhibitors exert part of their beneficial effects via post‐glomerular vasodilation, 21 , 22 , 23 which is also one major nephroprotective action of ACEI/ARBs. Combining these two drug classes therefore possibly has an additive effect regarding renal haemodynamic function.…”

Home Blood Pressure-based Guidance Did Not Increase Anti-albuminuric Effects on Diagnostic Provision of Microalbuminuria in School Workers: A Miyagi Karoshi Prevention Study

“…It is difficult to explain this mechanism in the non-guided group. Because eGFR was significantly decreased without significant changes in BP one year later, medications that decrease glomerular pressure, such as RAS or SGLT2 inhibitors might be promoted ( 30 ). Further studies are needed to confirm this hypothesis.…”